胃肠道神经内分泌肿瘤的影像学表现与病理分级

目的:探讨胃肠道神经内分泌肿瘤的影像特征并预测病理分级的价值。方法:回顾分析14例胃肠道神经内分泌肿瘤患者的影像学表现及临床资料。将肿瘤的病理分级分为神经内分泌瘤NET组(包括G1级、G2级)及神经内分泌癌NEC组(G3级)。根据肿瘤的CT及MRI表现,分析两组之间差别。结果:肿瘤位于食管1例,胃2例,小肠4例,阑尾2例,结肠3例,直肠2例。NET组10例中G1级6例,G2级4例;NEC组G3级4例。结论:胃肠道神经内分泌肿瘤有一定的影像学特征,肿瘤大小、形状、边缘、均质程度、外侵和转移等可以在术前预测其病理分级。     

胰腺神经内分泌肿瘤放射性核素治疗

胰腺神经内分泌肿瘤（pNENs）是最常见的神经内分泌肿瘤。对于早期局限的pNENs,手术是主要的治疗手段并可达到治愈的效果,但对于无法手术切除或已经发生远处转移的pNENs,因pNENs常过表达生长抑素受体,肽受体介导的放射性核素治疗（peptide receptor radionuclide therapy,PRRT）或可作为一线治疗方案。近年来关于PRRT用于pNENs的临床试验研究逐年增多,许多报道证实了90Y及177Lu标记的生长抑素类似物在pNENs病人中的良好疗效。     

喉部小细胞神经内分泌癌患者长期无病生存1例报告及文献复习

目的：分析长期无病生存的喉部小细胞神经内分泌癌（LSCNC）患者的临床特点,为LSCNC的诊治提供依据。方法：收集1例原发性LSCNC患者的临床资料,结合相关文献,分析LSCNC和肺外小细胞癌（EPSCC）的临床特点、诊断及治疗方法。结果：患者为55岁男性,既往有长期大量吸烟及饮酒史,以颈部包块起病,行喉镜检查见会厌喉面左侧不平肿物;颈部肿物穿刺活检提示淋巴结转移癌。患者随后行喉切除术和双侧颈部淋巴结清扫术。术后病理诊断为LSCNC;免疫组织化学法检查,CD56（NK-1）（+）,CK-pan （+）,CgA （-）,Syn （-）,Ki-67（+90%）。患者术后行瘤床区及淋巴结引流区放疗加6个疗程依托泊苷和顺铂（EP）方案化疗,未行脑预防照射（PCI）。规律复查喉镜、头颅核磁等检查,未见复发和转移,目前仍存活,无病生存期已达38个月。结论：LSCNC恶性程度高,确诊主要依靠病理组织形态学和免疫组织化学检查。目前LSCNC多采用手术、化疗和放疗联合的综合治疗,不推荐应用PCI,综合治疗可以改善预后。     

Combined large cell neuroendocrine carcinoma

We report a case of combined large cell neuroendocrine carcinoma. A 78-year-old man with vertigo was referred to our hospital where chest X-ray revealed a tumor shadow in the right lung. A transbronchial lung biopsy specimen verified a diagnosis of non-small cell lung carcinoma (cT1N0M0). Right lower lobectomy with mediastinal lymph node dissection (#7,8,9) was performed. A postoperative histological diagnosis was combined large cell neuroendocrine carcinoma of a component of squamous cell carcinoma [pT4 (pm) N2M0]. The patient received concurrent chemoradiotherapy due to upper mediastinal lymph node metastasis 4 months after surgery. The chemoradiotherapy well responded and the patient remains well 9 months after surgery.     

Small cell neuroendocrine carcinoma of the prostate: incidence and a report of four cases with an examination of KIT and PDGFRA

Because there have been no reports on the incidence and expressions and mutations of KIT and PDGFRA in small cell neuroendocrine carcinoma (SCNEC) of the prostate, the author surveyed archival specimens of 2,642 prostatic specimens (biopsy, 1,503 cases; transurethral resection, 1,009 cases; prostatectomy, 130 cases). Of these, 706 cases were malignant tumors. In equivocal cases (n = 16) of Gleason 5 adenocarcinoma resembling SCNEC, several neuroendocrine markers were immunohistochemically examined. As the results, four cases of SCNEC were identified; therefore the incidence of SCNEC was 0.5% of all prostatic malignancies. All the four cases were biopsies. The remaining 686 cases were adenocarcinomas. In case 1 (50 years of age), the SCNEC tumor cells were positive for cytokeratin, P504S, synaptophysin, KIT, and PDGFRA, but negative for PSA, neuron specific enolase, CD56, and TTF‐1. In case 2 (70 years of age), the tumor cells were positive for cytokeratin, PSA, P504S, chromogranin, and synaptophysin, but negative for neuron‐specific enolase, CD56, TTF‐1, KIT, and PDGFRA. In case 3 (72 years of age), the SCNEC tumor cells were positive for cytokeratin, PSA, P504S, synaptophysin, CD56, KIT, and PDGFRA, but negative for neuron‐specific enolase, chromogranin, and TTF‐1. In case 4 (81 years of age), the SCNEC tumor cell were positive for cytokeratin, PSA, P504S, chromogranin, synaptophysin, neuron‐specific enolase, KIT, and PDGFRA, but negative for CD56 and TTF‐1. A molecular genetic analysis using PCR‐direct sequencing showed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes in three informative cases of SCNEC. The present cases were the first of prostatic SCNEC with an examination of KIT and PDGFRA expression and KIT and PDFGRA gene mutations. Prostate 72:1150–1156, 2012. © 2011 Wiley Periodicals, Inc.     

Neuroendocrine expression in node positive prostate cancer: correlation with systemic progression and patient survival

PURPOSE: Neuroendocrine cells are ubiquitous but uncommon in benign and neoplastic prostate epithelium, and they are considered important for regulating cell growth and differentiation. The predictive value of neuroendocrine immunoreactivity for patient outcome after radical prostatectomy is uncertain. In this study we determined the expression of 2 important neuroendocrine markers, chromogranin and serotonin, in benign epithelium, primary prostate cancer and lymph node metastases, and correlated cellular expression with patient outcome. MATERIALS AND METHODS: We studied 196 patients with node positive prostate adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years (range 0.3 to 11). The cellular expression of chromogranin and serotonin in matched samples of benign tissue, primary prostate cancer and lymph node metastases from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, pathological findings (Gleason score, DNA ploidy and cancer volume) and patient outcome, including clinical progression, cancer specific and all cause survival. RESULTS: Chromogranin immunoreactivity was greater in benign prostatic epithelium and primary cancer cases (99% each) than in those of lymph node metastases (37.5%) (pairwise comparisons with metastases p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 6% (median 5%), 6% (median 3%) and 2.2% (median 0%), respectively. Serotonin immunoreactivity was greatest in benign prostate epithelium cases (98.5%) with less in primary cancer (95%) and lymph node metastases (21.5%) (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 2.2% (median 3%), 2.4% (median 2%) and 0.4% (median 0%), respectively. Chromogranin expression was invariably greater than that of serotonin for all 3 diagnostic categories (p <0.0001). There was a marginally significant positive trend in the level of chromogranin expression in benign prostatic epithelium and systemic progression (p = 0.05) but no significant association with cancer specific or all cause survival (p >0.1). No significant association was observed of chromogranin expression in primary cancer or lymph node metastases with any patient outcomes (p >0.1). There was a significant association of the level of serotonin expression in benign prostatic epithelium with cancer specific survival (p = 0.03) but no significant association with systemic progression or all cause survival (p > 0.1). There were positive trends in the association of serotonin immunoreactivity in primary cancer with systemic progression (p = 0.09) and cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No significant association was observed of serotonin expression in lymph node metastases with any patient outcomes (p >0.1). CONCLUSIONS: Benign prostatic epithelium and primary prostate cancer express a significantly greater number of chromogranin and serotonin immunoreactive cells than lymph node metastases, suggesting that decreased expression of neuroendocrine markers is involved in cancer progression. However, neuroendocrine expression was marginally useful for predicting the outcome in patients with node positive prostate cancer treated with radical prostatectomy.     

Ureteral carcinoid tumor

Most ureteral tumors are transitional cell neoplasms. Neuroendocrine tumors of the genitourinary tract are extremely rare. To our knowledge, only one ureteral carcinoid tumor has been reported before. We report a second case of ureteral carcinoid tumor found in a 70-year-old female.     

Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism

BACKGROUND: Melatonin, the main secretory product of the pineal gland, inhibits the growth of several types of cancer cells. Melatonin limits human prostate cancer cell growth by a mechanism which involves the regulation of androgen receptor function but it is not clear whether other mechanisms may also be involved. METHODS: Time-course and dose-dependent studies were performed using androgen-dependent (LNCaP) and independent (PC3) prostate cancer cells. Cell number, cell viability, and cell cycle progression were studied. Neuroendocrine differentiation of these cells was evaluated by studying morphological and biochemical markers. Finally, molecular mechanisms including the participation of melatonin membrane receptors, intracellular cAMP levels, and the PKA signal transduction pathway were also analyzed. RESULTS: Melatonin treatment dramatically reduced the number of prostate cancer cells and stopped cell cycle progression in both LNCaP and PC3 cells. In addition, it induced cellular differentiation as indicated by obvious morphological changes and neuroendocrine biochemical parameters. The role of melatonin in cellular proliferation and differentiation of prostate cancer cells is not mediated by its membrane receptors nor related to PKA activation. CONCLUSIONS: The treatment of prostate cancer cells with pharmacological concentrations of melatonin influences not only androgen-sensitive but also androgen-insensitive epithelial prostate cancer cells. Cell differentiation promoted by melatonin is not mediated by PKA activation although it increases, in a transitory manner, intracellular cAMP levels. Melatonin markedly influences the proliferative status of prostate cancer cells. These effects should be evaluated thoroughly since melatonin levels are diminished in aged individuals when prostate cancer typically occurs.     

Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine neoplasms include well-differentiated pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine carcinomas (NECs) with well-differentiated PanNETs accounting for most cases. Other pancreatic primaries and metastatic carcinomas from other sites can mimic pancreatic neuroendocrine neoplasms. Immunohistochemical studies can be used to aid in the differential diagnosis. However, no specific markers are available to differentiate PanNETs from NETs of other sites. Although NECs are uniformly deadly, PanNETs have variable prognosis. Morphology alone cannot predict the tumor behavior. Although some pathologic features are associated with an aggressive course, Ki67 is the only prognostic molecular marker routinely used in clinical practice.